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so far i have been in n letrozole since march with a 3 week break because of BP issues, no sides effects, and i hope none for a good long time. I cannot do tamox due to blood clot issues,
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I was told that tamox was contraindicated for me due to my family cardiovascular history being a virtual train-wreck. (BC came as a shock to me, because I’d always thought that it would be my heart, arteries or lungs that would get me—or maybe a drug-resistant bug because of allergies to three major classes of antibiotics). Also, the only antidepressant that works well for me w/o SEs is also contraindicated if taking tamox. because the former interferes w/the latter’s enzymatic pathway. I’m 10 years post-menopausal, so AI was what was prescribed. Letrozole is no picnic, but neither is it the torture many patients here report with it or other AIs. All endocrine therapy is designed to reduce the amount of systemic estrogen (though tamox. alone doesn’t mess with its production). In the absence of functioning ovaries, estrogen is made by the enzyme aromatase converting the androgens produced by fat cells and adrenal glands into estrogen. So as a mild-to-moderately obese woman, without an AI I would have more estrogen in my body than would a thinner woman, and it would be tougher for tamox. to do its job of blocking tumor cells’ access to it.
Zometa questions:
1. Starting 2 nights before my infusion, I switched my bedtime antihistamine from Zyrtec to Claritin, and took it for a week thereafter. Because I am skeptical of the “non-drowsy” claims, I always take my antihistamine at bedtime, so I have no trouble functioning on it. (I also have 3-4 cups of black coffee or shots of espresso a day, which may help alertness as well as keep my lungs open).
2. Why the timing of dental work either 2 months before or 2 months after Zometa? Infused bisphosphonates (Zometa, Reclast) and injected biologics (Prolia, Xgeva) increase the risk of osteonecrosis (basically death of the bone) of the jaw (ONJ). Nobody knows why, but they do— and when it happens it’s a bee-yotch and it’s irreversible. Oral bisphosphonates (Fosamax, Actonel, Boniva) don’t—but they do cause GERD (and aggravate pre-existing GERD, pushing it over the edge into erosive esophagitis, or Barrett’s Esophagitis—a precursor to esophageal cancer, which few people survive); and unlike the infused and injectables, do not have any effect on mets, just osteoporosis/osteopenia. And the infused bisphosphonates do seem to increase the risk for paradoxical horizontal femoral (thighbone) fractures—“paradoxical” because this is the kind of stuff that you take bone drugs to prevent. Moreover, latest research presented at the AAFP conference shows bisphosphonates (oral or infused) strengthen only vertebrae, not weight-bearing long bones (tibia, fibula, and femur—including the femoral neck and acetabulum—the “ball” in the hip joint socket, and the upper part of the femur that culminates in the ball). Only the injectable biologics do that—and there is oncological research showing they’re also superior in preventing, delaying the onset of and slowing the progress of bone mets. Flip side is that they’re crazy-expensive and immunosuppressive (so you could end up with serious infections or even bone marrow cancers such as MDS/leukemia/myeloma, though that’s a very remote risk).
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Bisphosphonates: Bone Strengtheners or Bone Hardeners?
by Lane Lenard PhD on 13/02/10 at 1:39 pm
by Lane Lenard, PhD
Bisphosphonates are now the most widely marketed and prescribed patented, FDA-approved anti-osteoporosis drugs. Bisphosphonates mimic, to some extent, the effects of estrogen on bone in that they work by inhibiting bone resorption [the process by which old bone is removed to make room for new bone]. However, like estrogen, these drugs have no ability to build new bone.
Currently FDA-approved bisphosphonates, including Fosamax (alendronate), Actonel (risedronate), Didronel (etidronate), Boniva (ibandronate), and Reclast (Zometa) (zoledronate), are designed to strengthen bone by inhibiting normal osteoclastic bone resorbing activity, which slows the loss of bone mineral density (BMD), allowing the trabecular architecture to stabilize. Notice that this has nothing to do with stabilizing the balance between estrogen and progesterone, restoring calcium levels, or any other natural process.
Like many other patented drugs, bisphosphonates are synthetic analogs of an important natural bone-building chemical, pyrophosphate, which normally helps bind calcium to bone tissue through a process known as mineralization. Unlike pyrophosphate, however, bisphosphonates actually block normal mineralization as well as osteoclastic bone resorption.
Large, placebo-controlled trials generally show that these drugs can indeed increase BMD and reduce the risk of vertebral, hip, and other nonvertebral fractures in women with osteoporosis—at least in the short run. That's the good news. Merck, the company that markets the leading bisphosphonate, Fosamax (now also sold generically as alendronate), seized upon results like these to turn its drug into a blockbuster worth as much as $3.6 billion per year. Use of Fosamax and other bisphosphonates has been growing at an especially rapid rate since 2002, when the publication of the Women's Health Initiative (WHI) results scared women away from "estrogen" replacement, which until then had been the leading conventional method for preventing osteoporosis.
Unfortunately, all may not be so rosy after all. Trials lasting up to 10 years are beginning to raise doubts about the long-term safety and efficacy of bisphosphonates. The main problem is that bisphosphonates not only directly—and unnaturally—inhibit osteoclastic bone resorption, they also indirectly inhibit the other side of the bone-building coin, osteoblastic bone formation.
How Bisphosphonates Work
In normal bone remodeling, osteoclasts first resorb bone tissue, forming little pits in the bone structure. In short order, osteoblasts come along—like microscopic road repair crews—to fill in those pits with healthy new bone. Under normal circumstances, osteoblasts remain inactive until the osteoclasts first do their thing. If osteoclastic activity is suppressed enough, though, as it is by bisphosphonates, osteoblasts have no cavities to fill, and so formation of new bone ceases. Although estrogens also inhibit osteoclastic activity, they do so in a natural way that does not suppress osteoblastic bone building, which can still be stimulated by agents like progesterone, testosterone or strontium.Thus, the physical cost of bisphosphonate-induced bone stabilization is to freeze normal bone remodeling—a highly unnatural state of affairs.
The Long Term Consequences of Suppressing Normal Bone Remodeling
What does this mean for bone health in the long term? This is a crucial question, because there's no such thing as short-term treatment with these drugs. A woman who starts taking bisphosphonates at age 55 could easily still be taking them 25 or 30 years later, if she stays healthy and can tolerate them. The longest trial so far reported—10 years with Fosamax—apparently evidenced no increase in fracture rate in the later years. However, the design of this Merck-sponsored study has been criticized.Another much smaller clinical trial – conducted independently of direct drug company influence—presented a very different story. The researchers followed 9 women with osteopenia or osteoporosis, who had been taking Fosamax for 3 to 8 years (some had also been taking Premarin) and had developed nonspinal fractures (to the lower back, ribs, hip bones, and femur) while performing normal daily activities such as walking, standing, or turning around. The locations of these fractures were unusual for women with osteoporosis, and none of the fractures was related to a fall or other trauma. The fractures occurred earlier in the women taking both Fosamax and Premarin, suggesting an additive effect on bone resorption.
Since the women continued taking Fosamax while their fractures were healing, the researchers took the opportunity to study the drug's effects on the healing process. What they found was not encouraging. In most of the women, fracture healing slowed down considerably, taking months or even years longer than it should have. One woman's broken hip (femoral shaft fracture) took more than two years to heal, despite the fact that her doctors had treated the fracture aggressively, employing metal screws and rods as well as a bone graft. In most of the women, once the drug treatment was discontinued, the fractures healed satisfactorily.
The researchers also performed bone biopsies at a site away from the fractures, which was intended to give them an idea of the health of the women's bones in general. They found a strikingly severe depression of bone formation—nearly 100-fold lower in some of the patients than has been found in healthy postmenopausal women. They concluded that the deterioration in bone health was almost certainly due to Fosamax treatment, and that it was probably exacerbated by the coadministration of Fosamax with estrogen, since both suppress bone turnover.
One Woman's Experience with Fosamax
In one case reported in the medical literature, Jennifer P. Schneider, MD, PhD, a physician from Tucson, Arizona, described her personal experience with Fosamax. At age 59, Dr. Schneider, who had gone into menopause prematurely in her early 40s, was riding in a New York City subway when the car jolted. Although the femur is normally one of the strongest bones in the body, she reported in the journalGeriatrics that when the car lurched, she "shifted all her weight to one leg, felt the bone snap, and fell to the floor of the train." The photograph shows an X-ray of Dr. Schneider's shattered femur.At the time of her fateful subway ride, Dr. Schneider had been experiencing pain in her right thigh for about 3 months, and a bone scan the week before had shown a stress fracture of her right femur. She had also been taking Fosamax for about seven years, in addition to calcium and conventional HRT (Premarin + Provera).
After the fracture, her doctors persuaded her to continue taking Fosamax, dismissing her concerns about its potential for suppressing bone turnover—that is, healing—as only "a theoretical possibility." Yet despite aggressive treatment over more than nine months, including electrical bone stimulation and two surgeries to implant increasingly larger metal rods, her fracture refused to heal. Finally, she halted the drug on her own, and within six months the pieces of her broken thighbone finally began to unite.
Dr. Schneider remained off Fosamax for two years, during which time she was able to regain her normal level of activity. However, since her bone scans were showing that her BMD was beginning to decline somewhat, her doctors advised her to start taking Fosamax again. Reluctantly, she agreed. About a year later, though, upon getting out of bed one morning, she felt a pain in her right foot with each step. Fearing the possibility of another nontraumatic stress fracture, she again stopped taking the Fosamax, but a bone scan 2 months later revealed that she had indeed suffered a stress fracture in her foot (the second metatarsal bone).
For the second time in 4 years, Dr. Schneider had fractured a bone due to no particular trauma. This time, instead of Fosamax, she started taking calcium supplements, oral estradiol and oral micronized progesterone [natural progesterone in pill form]. Wearing sturdy shoes to support her foot, she started walking a mile every day, and after several months, her fractured foot finally healed. Remaining on this regimen ever since, she has not suffered any new fractures.
Dr. Schneider is not alone in her fracture experience. After she published her own "case" history in 2006, she was sent numerous unpublished reports of others who had had similar fractures. Continuing to research the issue, she recently reviewed the current knowledge about this phenomenon. Meanwhile, two other papers—one from doctors in Singapore and the other from the Hospital for Special Surgery in New York—have independently documented a total of 87 men and women, who had had "low-energy," "low-impact," "fragility," or "atypical" fractures associated with use of Fosamax or other bisphosphonates. It appears that these unusual fractures have several things in common:
- Most patients had been taking Fosamax for 4 to 7 years prior to the event.
- The fracture was often preceded by localized pain in the thigh for 1 week to 2 years.
- Some patients had sustained fractures in their opposite femur 2 to 4 years earlier.
- The fractures were associated with "low-energy" events, like tripping, and patients often could feel the bone snap prior to the fall.
Patients with bisphosphonate-related femoral shaft fractures often show a specific and unusual fracture pattern that is visible on X-rays. In one survey of men and women admitted to a trauma center, 70 such fractures were identified over a 5‑year period. The unusual X-ray pattern was seen in only 1 patient who was not being treated with Fosamax. In other words, the unusual fracture pattern was specific to 98% of Fosamax patients.15
Perhaps the oddest aspect of these Fosamax-related fractures is that they tend to occur in the upper femur. Remember, this bone is composed primarily of hard, thick cortical bone, and it is usually the strongest bone in the body. In most healthy people, femoral fractures like these occur only after major, high-energy trauma, like a fall from a high place or an automobile accident. This is in sharp contrast to typical osteoporosis-related fractures, which occur in relatively soft, weakened cancellous bone (for example, trochanter of the hip, wrist, ribs) following (or sometimes preceding) relatively mild trauma, like tripping and falling. As Dr. Schneider points out in her recent review, the femur is "unlikely to fracture in low-energy trauma unless extreme osteoporosis is present.14 The reports of multiple cases of low-impact femoral fractures in patients taking alendronate [Fosamax] for several years, a previously rare event, have therefore called for further study of the possible connection between alendronate and such fractures."13\
How Bisphosphonates Might Promote New Fractures
Given the way that bone remodeling normally takes place, it's easy to see why bisphosphonates might inhibit fracture healing (even though many doctors have been reluctant to admit it), but how they could actually promote new fractureswhile they're supposed to be preventing them seems less obvious. Current thinking on this paradox goes as follows:The typical stresses of every day life tend to cause bones to develop microcracks. Under normal conditions in otherwise healthy people, these microcracks trigger osteoclasts and osteoblasts to spring into action to repair the damage, unnoticeably and with no ill effects. However, if bone remodeling (turnover) is strongly inhibited, as it unquestionably is by bisphosphonates, the osteoclasts and osteoblasts cannot do their jobs, and so, the microcrack damage—like a well-traveled but poorly maintained road pounded by heavy traffic over many years—develops ever-widening cracks and potholes. This hypothesis has recently been supported by Czech researchers, who found that, in women with low BMD, Fosamax treatment—which keeps the body's "road repair crews" off the job—led to an increase in the accumulation of microcracks.
Let's be clear about something: despite the fact that Fosamax increases BMD, it may still make bones more likely to fracture in the long term. In lab animals, Fosamax-induced oversuppression of bone remodeling increased the appearance of microcracks by 2- to 7‑fold. Accumulation of these microcracks, without subsequent repair—due to the actions of bisphosphonates—appears to increase the risk of fractures while delaying or inhibiting healing.
In summary, even though bone strength appears toincrease due to Fosamax treatment, in fact, use of this patented medicine has been associated with a 20% reduction in bone toughness (that is, its ability to endure bending pressure without breaking). Dr. Susan M. Ott of the University of Washington, Seattle, compares bisphosphonate-treated bone to an old tree. Under the stress of a strong wind, younger trees are flexible enough to bend easily without breaking. However, older, denser trees, faced with a serious windstorm, are less able to bend and might just snap in two. "Many people believe that these drugs are 'bone builders,'" she wrote in a letter to a medical journal, "but the evidence shows they are actually bone hardeners." (Italics added.)
In an editorial in the Journal of Endocrinology and Metabolism, Dr. Ott suggested that bone tissue in Fosamax-treated women resembles a form of "adynamic bone disease" sometimes seen in people whose kidneys are failing. She notes that, once ensconced in bone tissue, bisphosphonates virtually never leave, and in fact, they accumulate with use. "These drugs are not metabolized, but are either excreted renally [in urine] or deposited within bones. … There is no known method of removing the medication from the bones," she wrote.
Dr. Ott urges caution in the long-term use of bisphosphonates, pointing out that research supports their beneficial effects—but only for the first 5 years. "I believe the current evidence suggests that bisphosphonates should be stopped after 5 years." She added, "The bisphosphonates in doses used today suppress bone formation to a greater extent than the other anti-resorbing medications, so it is possible that microdamage accumulation would develop after 15 or 20 years—just about the time between menopause and the usual onset of osteoporotic fractures."
More Bisphosphonate Bad News:It's Not Just in Your Bones
GI Toxicity (or How to Lie with Valid Clinical Trials)
As if these problems weren't bad enough, bisphosphonates are also potentially destructive to the upper gastrointestinal (GI) tract, including the mouth, esophagus, stomach, and possibly jawbone. As noted in the official FDA-approved Fosamax label, "Fosamax, like other bisphosphonates, may cause local irritation of the upper gastrointestinal mucosa. Esophageal adverse experiences, such as esophagitis, esophageal ulcers, and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with Fosamax. In some cases, these have been severe and required hospitalization." Recent reports have even linked its use to cancer of the esophagus.It's hard to know just how common these kinds of GI complications are. In Merck's original clinical trials, for example, there was little difference in the frequency of GI side effects between the Fosamax and placebo groups. However, in the real world of physicians and patients, GI side effects of Fosamax and other bisphosphonates are a serious problem.22
Is Merck fudging the data about GI complications? Not really. What we have here is a perfect example of how a large-scale, well-controlled, FDA-approved, drug-company-sponsored clinical trial can do everything right and still distort reality by making a drug look safer than it really is. Here's how it works:
Serious as the bisphosphonate-related GI side effects are, it's pretty simple to prevent them by closely following the recommended procedures for taking the drug, all of which are basically designed to get the pill out of your mouth, through your esophagus, and into and out of your stomach as quickly as possible, with as little contact as possible with the delicate linings of these organs. To accomplish this and also to maximize absorption, Merck recommends the following:
- Take Fosamax first thing in the morning, right after getting out of bed and at least 30 minutes before ingesting any other food, beverage, or medication.
- Take Fosamax with a full glass (6-8 oz) of ordinary water, but not mineral water.
- After swallowing the Fosamax pill, drink another 2 oz (¼ cup) of water.
- Do not lie down for at least 30 minutes and not until after eating your first food of the day—at least 30 minutes later.
Taking Fosamax with too little water can expose the esophageal or gastric (stomach) lining to the dangerously irritating drug, which can cause anything from heartburn to perforated ulcers to cancer. Lying down with the drug still in your stomach risks reflux of the acidic, drug-loaded gastric contents back into the esophagus, where they can do serious harm. Moreover, taking Fosamax while food or other meds are still in your stomach significantly reduces the drug's absorption, thus inhibiting its effectiveness. Even the minerals in mineral water can impede Fosamax absorption.
So, after taking Fosamax in the morning, there's no going back to bed for at least 30 minutes (What do you do during this time? Watch TV? Take the dog for a walk? Read a book?); nor are you supposed take it before bedtime at night. You can't even take the drug and then have your morning cup of coffee or tea. You must take it on an empty stomach, so you need to wait at least half an hour before consuming anything else. Any deviations from these very stringent procedures can reduce the drug's "therapeutic" effects and/or increase the chances it will cause serious injury to the lining of your upper GI tract.
Clearly, then, taking Fosamax and other bisphosphonates is a far cry from popping an ordinary pill in the morning. These drugs demand a commitment to religiously following the recommended procedures or you face potentially dire consequences. For older people, who typically take lots of other meds at different times each day and who may get easily confused about which is which, Fosamax may be a prescription for disaster. To get around these problems, companies have been designing new bisphosphonate drugs that can be taken once a week (e.g., Fosamax), once a month (e.g., Boniva), or even once a year (Reclast – by IV infusion).
Now, back to the clinical trials. We know that the people who run clinical trials for pharmaceutical companies go out of their way to make sure their participants follow the recommended drug-taking rules to a T. Therefore, it's no surprise that Merck didn't see very many serious side effects during its clinical trials, compared with placebo, thus allowing it to claim—statistically speaking—that the drug was safe.
Not so, though, for people who get their prescriptions from the average harried, conventional HMO GP, who may not have the time, understanding, or motivation to carefully instruct his/her patients and to follow up on their drug-taking in a timely manner. More likely, it's, "Take these pills and come back in 3 to 6 months. Oh, and be sure to read this booklet about the right and wrong ways to take the pills. What did you say your name was?"
Under such real-world circumstances, bisphosphonate-related GI pathology turns out to be a common and potentially very serious problem. In fact, the FDA has recently reported receiving more than 40 case reports of esophageal cancer related to Fosamax use, of which 14 resulted in a patient's death. Another 31 cases of esophageal cancer (and 6 deaths) linked to use of Fosamax and other bisphosphonates have been reported in Europe and Japan. The median time from initial drug exposure to cancer diagnosis was just 2.1 years in the US and 1.3 years in Europe and Japan.
Beware "Jaw Death"
Recently, a new, very disturbing, rare bisphosphonate side effect—osteonecrosis of the jaw (ONJ), also known as jaw death—has emerged. In ONJ, the bone tissue in the jaw fails to heal after minor trauma, such as a tooth extraction, which leaves the bone exposed and vulnerable to a particularly difficult-to-treat bacterial infection and fracture. Long-term antibiotic therapy and surgery to remove dying bone tissue may be required. Occasionally, a large portion of the jaw may have to be removed.Ordinarily, ONJ is uncommon and is primarily associated with cancer chemotherapy, radiation of the head or neck, steroid therapy (e.g., cortisone), poor dental health, gum disease, dental surgery, alcohol abuse, and other conditions. Accustomed to 1 or 2 cases a year, doctors at one hospital were alarmed to notice that, over a 3‑year period, ONJ had been diagnosed in 63 of their patients. The one thing all these patients had in common was bisphosphonate treatment. While 56 of them (89%) had been receiving IV bisphosphonates (pamidronate or zoledronate) as cancer chemotherapy for at least a year, 7 of the patients (11%) had been taking only oral bisphosphonates (alendronate or zoledronic acid) at standard doses for osteoporosis.
While there have been numerous subsequent anecdotal reports of bisphosphonate-related ONJ, Merck, along with the American Dental Association, continue to insist that oral Fosamax (as well as other bisphosphonates) poses minimal risk of ONJ. However, a recent systematic study from researchers at the University of Southern California School of Dentistry suggests otherwise. They evaluated the electronic medical records of patients attending the USC dental school clinic to find out which ones had ever used Fosamax and which of those later developed ONJ. Of the 208 patients (all women, aged 63 to 80) with a history of once-a-week Fosamax use, 9 were being treated for ONJ – about 4%. (Four cases were associated with tooth extractions, and five with ulceration related to poorly fitting dentures.) This was a far higher incidence than had been suggested by most "authorities." By contrast, of the 4,384 USC patients who had undergone dental extraction but had never used Fosamax, not a single one developed ONJ.
"We've been told that the risk with oral bisphosphonates is negligible, but 4% is not negligible," insisted Dr. Parish Sedghizadeh, who led the USC research team. He points out that most doctors who prescribe bisphosphonates do not tell their patients about the drugs' potential risks, even with short-term use.
The problem is that, as Dr. Ott suggested above, the drug remains locked into bone tissue for a long time (it may take 10 years for levels to drop by half even once you stop taking it). Thus, continuous use allows the drug to build up to levels previously thought to be achievable only by high-dose intravenous administration to cancer patients. The USC results showed that ONJ could develop after taking oral Fosamax for as little as 1 year.
Several lawsuits have been filed against Merck alleging that Fosamax causes ONJ and that Merck has known about the risk but has been keeping it under wraps. "We're not quite sure what we're dealing with over the long haul," Dr. Susan Ott told the Los Angeles Times. "Side effects like this should make ordinary, healthy women think twice."
Increased Heart Risks, Too
The latest bad news about bisphosphonates concerns their adverse effects on heart function. New research shows that women who have ever used Fosamax or Reclast (also called Zometa) double their risk of developing serious atrial fibrillation (AF), a form of heart arrhythmia. Common symptoms include light-headedness, palpitations, chest pain, and shortness of breath; or there may be no symptoms at all. Untreated AF can lead to fluid collecting in the lungs (pulmonary edema), congestive heart failure, and formation of blood clots that may travel to the brain and cause a stroke. An analysis of three studies covering more than 16,000 women, most of whom were taking the drugs for osteoporosis, found that 2.5% to 3% experienced atrial fibrillation; 1% to 2% experienced serious AF, leading to hospitalization or death.This article was reprinted with permission of the Townsend Letter, the Examiner of Alternative Medicine. It was also extracted, in part, from the book Stay Young and Sexy with Bioidentical Hormone Replacement by Jonathan Wright MD and Lane Lenard PhD (Smart Publications, 2010).
Notes
1. Hosking D, Chilvers CE, Christiansen C, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N Engl J Med. 1998;338:485–492.
2. Rosen CJ. Clinical practice. Postmenopausal osteoporosis. N Engl J Med.2005;353:595–603.
3. Chemical analogs are molecular look-alikes, but with subtle differences, like the substitution of a carbon atom for an oxygen atom. Bisphosphonates are analogs of the natural substance pyrophosphate in the same way that Provera is an analog ofprogesterone.
4. Smith A. Merck sales dip; Vioxx blamed [Web page]. CNNMoney.com http://money.cnn.com/2005/04/21/news/fortune500/merck/index.htm. 2005. Accessed April 24, 2006.
5. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med.2004;350:459–468.
6. Reginster JY, Deroisy R, Dougados M, Jupsin I, Colette J, Roux C. Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS trial. Osteoporos Int.2002;13:925–931.
7. Bone HG, Hosking D, Devogelaer JP, et al. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189-1199.
8. Roux C, Fechtenbaum J, Kolta S, Isaia G, Andia JB, Devogelaer JP. Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis. Ann Rheum Dis. 2008;67:1736–1738.
9. The researchers had grants from the US Public Health Service and the University of Texas Southwestern Medical Center, Dallas.
10. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–1301.
11. Schneider J. Should bisphosphonates be continued indefinitely? An unusual fracture in a healthy woman on long-term alendronate. Geriatrics. 2006;61:31–33.
12. She later switched to a patented combination of oral estradiol plus a progestin (norethindrone acetate), brand name Activella.
13. Schneider J. Bisphosphonates and low-impact femoral fractures: Current evidence on alendronate-fracture risk. Geriatrics. 2009;64:18–23.
14. Goh SK, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007;89:349–353.
15. Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma.2008;22:346–350.
16. Stepan JJ, Burr DB, Pavo I, et al. Low bone mineral density is associated with bone microdamage accumulation in postmenopausal women with osteoporosis.Bone. 2007;41:378–385.
17. Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab.2005;90:1897–1899.
18. Brody J. Plotting to save the structure of those aging bones. The New York Times.July 5, 2005.
19. Ott S. New treatments for brittle bones. Ann Intern Med. 2004;141:406–407.
20. Fosamax (alendronate sodium). Prescribing Information [Web page]. Merck & Co. Inc. http://www.fosamax.com/alendronate_sodium/fosamax/consumer/product_information/pi/index.jsp?WT.svl=1. Accessed April 26, 2006.
21. Wysowski DK. Reports of esophageal cancer with oral bisphosphonate use. N Engl J Med. 2009;360:89–90.
22. Greenspan SL, Harris ST, Bone H, et al. Bisphosphonates: safety and efficacy in the treatment and prevention of osteoporosis. Am Fam Physician. 2000;61:3731–2736.
23. Chustecka Z. Esophageal cancer in patients taking oral bisphosphonates [Web page]. Medscape Medical News. 2008. http://www.medscape.com/viewarticle/586127.24.
24. Basu N, Reid DM. Bisphosphonate-associated osteonecrosis of the jaw.Menopause Int. 2007;13:56–59.
25. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62:527–534.
26. Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2008;139:1674–1677.
27. Sedghizadeh PP, Stanley K, Caligiuri M, Hofkes S, Lowry B, Shuler CF. Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw: an institutional inquiry. J Am Dent Assoc. 2009;140:61–66.
28. Paddock C. Osteoporosis drug linked to bone death in jaw [Web page]. Medical News Today. January 5, 2009. http://www.medicalnewstoday.com/articles/134381.php.
29. Marsa L. Bone drugs' reverse danger. Los Angeles Times. April 3, 2006. Available at: http://www.latimes.com/features/health/la-he-fosamax3apr03,0,3944007,full.story?coll=la-headlines-business. Accessed April 27, 2006.
30. Heckbert SR, Li G, Cummings SR, Smith NL, Psaty BM. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med. 2008;168:826–831.
31. Miranda J. Osteoporosis drugs increase risk of heart problems. Presented at: CHEST 2008: the 74th annual assembly of the American College of Chest Physicians; October 25–30, 2008; Philadelphia, PA.
20 Responses to "Bisphosphonates: Bone Strengtheners or Bone Hardeners?"
Andrei
Apr 25th, 2011
Question for Barbara regarding treatment for ovarian cancer – what was the type and grade of your ovarian cancer and how was it treated?
Thank you
Janice Luft
Oct 17th, 2010
I am not surprised by this news. Which does not mean I am against prescriptive medications that save lives, and are just short of a miracle.I experienced via a friend the difficult side effects of "bisphosphonates" second hand.For several years I took a friend to a specialist for RA pain almost monthly. Because of the need to have some teeth extracted the once a month dose of the bisphosphonate was stopped, and so was the pain which was being treated on a regular basis – nearly every month with another drug that had negative long term effects on other organs, and could not be taken indefinitely.It was not minor pain that stopped when the bisphosphonate was stopped. It very intense pain. They'd hardly be able to bear walking or lifting their arms to put on a coat. It was heart breaking to see them suffer so much, and even more heart breaking to fight the push to put them back on the drug by medical professionals when it was clearly understood there was a connection to the drug.Doctors need to take their blinders off – along with Congress. We must embrace medications, with sound diagnostics based on digestive functioning so that there are minimal negative side effects for those taking them.We are impacting other species too with prescriptive drugs. Just look at what is happening to fish in the D.C. waterways. A reduction in dangerous dosages is necessary for even those not using them, because the honest reality is we all are taking them whether we like it or not. Same goes for everything we put out in the air – we all inhale from the industrial pale. It's not the earth that is in peril – it'll go on with or without us. We need to be proactive with sage wisdom: "Our food is our medicine and our medicine is our food".People need to be mindful that calcium does interfere with iron absorption and and the two should not be taken together for best results. Also sea vegetables have the highest levels of calcium and minerals. Three and a half oz. of milk has something like 140 ml. of calcium, compared to 1400 ml. in most sea vegetables – according to Paul Pitchford in his book "Healing with Whole Foods".Part of the problem with "Capitalism" is that there is not a full accounting of the cost which is passed on to the consumer, taxpayer, or future generations. And it's based, often, on exploiting resources, coupled with cheap labor.The Gold Rush is over, Timber's been cleared, Water's are gooey and murky, and the seeds have been sewn for a harvest of wealth via health… as always follow the money into the rabbit hole of "private equity" partnerships. Blah, blah, blah…God help us all.
Judy Weiland
Mar 21st, 2010
Im surprised this article did not include the issue of severe bone pain and hair loss experienced by many, including myself. I first started taking Fosamax in about 1999 and within a year it did show bone growth. But when the drug was changed to a generic form and I was forced by the insurance company to switch to the generic form, I experienced upper GI distress as well as bone pain and thinning hair. I was then switched to Boniva and the bone pain became severe. I went online and was surprised to read the many comments left from other women who were going through the same pain and distress. I was advised by my PCP to go off the drug and consider IV Aclasta, so I went online to research it and found a website with comments from women who stated it produced the same side effects of bone pain and hair loss . It is frightening …I spoke with my dentist who stated he had a patient in his office who was advised to have the IV Aclasta and wanted his opion on the health of her jaw … he found her to have no bone or oral issues. Within three months he found her sitting in his dental chair, unable to speak due to all the blisters in her mouth and down her throat that had occured after the infusion.
Barbara
Mar 19th, 2010
I have worked with a naturopath who insists that all degenerative disease (including osteoporosis) starts with a starving thyroid. Blood tests are unreliable so a normal range TSH doesn't necessarily equal a healthy thyroid. He does muscle testing to determine a deficiency of iodine, which is lacking in the American diet. (Iodized salt is harmful, as the aluminum weakens the thyroid, so don't depend on that for iodine.) My challenge is that I had a thyroidectomy and parathyroidectomy 15 years ago. Since then, I also had ovarian cancer, but declined chemo in favor of an alternative, natural approach. I've been cancer free for 6 years. Now, I have osteoporosis, and at the naturopath's recommendation I started on Miacalcin (synthetic salmon calcitonin). Calcitonin is essential for absorption of calcium. It's made by a healthy thyroid. I switched from Synthroid to Armour thyroid medication and hope to see results. Is there anyone out there with a similar profile? No thyroid or parathyroid who successfuly reversed osteoporosis?
Karena Thek Lineback
Feb 24th, 2010
great article. Sent it on to family and friends with osteoporosis. thanks for publishing and thank-you for listing your resources.
Nicola
Feb 19th, 2010
Am I glad to have read this article. Will give serious thought to following a more natural approach to dealing with my newly diagnosed osteoporosis – I had a gut feeling about rushing into taking alendronic acid and calcium supps. I am currently taking them on recommendation from GP. I think he had better read this!
Gloria
Feb 15th, 2010
Where does Evista fit into tall this?My doctor has been telling me I will need to start it at 60 ( I have ostopenia apparently and please excuse my spelling!)
Dr Joyce Block
Feb 15th, 2010
Thank you for publishing this well-researched, easy-to-read article. This information is extremely useful and I will send it to colleagues and friends.
Annemarie
Feb 14th, 2010
I feel sick after reading this article. I just had the IV infusion of Aclasta 5 days ago which is to last a year. I agonized over the decision on whether or not to take the drug. I'm 51 and my last bone density scan showed osteoporosis with a high risk of fracture. The endocrinologist offered me Forteo and/or Aclasta. It didn't take much research to know I wanted nothing to do with Forteo. I even decided against the Aclasta. But when I went to see him and asked for a year to see if I could increase my numbers using natural methods he told me bluntly I didn't have a year and could walk out of his office, fall and break a hip. Right now I'm feeling angry at myself for allowing myself to be manipulated. I know better. He knew what to say, what buttons to push to get someone like me, who takes no prescription drugs, to agree. I threw a lot of questions at him and he had an answer for everything. But after reading this I now know he wasn't giving me the whole story.
What has me confused is if I am wasting my time now by taking strontium, 10,000 IU vitamin D, calcium, bio-identical hormones etc. Is the Aclasta now stopping any good they would have done in rebuilding bone?
One thing is for certain. I will not be talked into another dose of Aclasta.
Thank you for providing this most informative article. I appreciate it
Ann Carter ANP
Feb 14th, 2010
I am a Family Nurse Practitioner who does mostly womens health using bio-identical. The one thing I emphasize is the us of testosterone. For the best of bone density, your estrogen, progesterone and testosterone have to be balanced. You can't have too much or too little without consequences, so be sure and get a saliva test done, which I have used in my practice for over 8 years (I use ZRT labs). With hormones, you must of a good balance, the key word is Balance. You will see more men getting osteopororsis as they are living longer, but not getting their testosterone replaced. Remember how bent over Pope John was before he died? He needed testosterone. Again, Balance, so get your hormones checked, including your thyroid and insulin and cortisol. Regards, Ann Carter
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Marijen, thanks for posting this. It is definitely worth reading even if it is on the long side. These drugs that are widely prescribed can be problematic for some people and everyone needs to have all of the facts. Excellent post!
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Thanks April, a fellow BCOer sent to me because I have several things going on, osteoporosis, trigger thumb, joint pain, and now a pulled something near my archilles heal. Maybe I should take the letrozole everyday other day, stop the calcium supplements. I don't know. My bone density doc said only three reclast infustions, no more. Maybe this is the reason. He doesn't explain anything. I also take D3 and K2. I'm lost here.
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Wow, you are really getting swamped with the A-Z. Have you tried a different AI yet? If not, maybe another drug would be easier on you? Although letrozole is rough, it beats exemestane for me by a little bit. Hopefully you can get some relief. Most of this stuff is so freaking painful. When your heel hurts, it is really rough. Hugs!
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That does it—no more Zometa for me, ever. I have difficult veins—it took 5 painful tries to start the I.V. and my arm was bruised for nearly a month. And I was sick as a dog for days after—so much so that I was prescribed Lyrica for the neuropathies that resulted. The only symptom I didn't get was bone pain, probably because I'd taken Claritin.
But what I'd like to see addressed is how osteopenia & osteoporosis caused by AIs in cancer patients can be ameliorated without these side effects, especially for those who can't do ballistic (e.g., running, jumping, jogging, impact-areobic dancing) weightbearing exercise. Are supplements enough? Must we stop taking other meds (e.g., PPIs, nasal steroids) we need to prevent erosive esophagitis and allergy-triggered asthma, in order to adequately absorb calcium? Obviously, estrogen helps—but we must minimize the estrogen our bodies already make, not take more of it. Do the injected biologics allow for bone formation and prevent these paradoxical fractures and ONJ, or do they have the same problems as bisphosphonates? (There's evidence ONJ risk is elevated with even the injected biologics—and they are immunosuppressive and can in rare cases cause secondary myeloid cancers).
My PCP told me he is against bisphosphonates, period—they simply don’t work. He is also skeptical of calcium supplementation in non-cancer patients, since even the most readily-absorbed forms are so poorly absorbed (the stomach’s homeostasis is remarkable) as to confer only infinitesimal (and theoretical) benefit—but concedes it’s necessary for patients taking AIs. He is also willing to go to bat for me in appealing my Part D carrier’s denial of coverage for Prolia.
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Hi Sandy,
You watching your vitamin D levels?
Some say folks with a prior cancer dx should keep them above 40 or 50.
Oh, consider avoiding all the common food culprits that deplete our nutrient availability and absorption - empty calories, sugar, alcohol, lack of fresh fruits and veggies, heavily processed foods. But for many, these comfort foods make life worth living and what's the use of being alive without our common and social comforts.
warm healing regards, Stephanie
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Been on this now for about a month after coming off anastrozole and bone are happier but now been hit with fatigue and shaky again. I rode my pony yesterday and been riding back now for nearly 12 months and yesterday had to sit down before unsaddling. No way i want to feel like this for another 4 years.
karenAus
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The article by Marijen has helpful information to consider, but it was written by an alternative medicine person wanting to sell bioidentical hormone replacement. I am not against alternative treatments, and do believe in complimentary treatments, but anyone reading that needs to consider that when weighing the information. I read all of that from a website 6 months ago when I decided to go ahead with Prolia. I'm glad I read it, because I think everything needs to be considered. For me, the potential benefits outweighed the risks, but for others, that may not be the case. It was not a decision I took lightly.
ChiSandy, Sorry you had such a horrible experience with Zometa. That's really rough. So far, I have not had problems with Prolia. I go for my second this week, so I have only had one so far, and perhaps side effects may take longer to develop.
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Over 3 1/2 years I have had no problem with Reclast infusion, even no flu symptoms. Had a five hour root canal retreat over two office visits and still no problem (three months before my last infusion. But if one of my bones snap I will feel different about it.
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I think that all of the pieces published regarding these drugs are worth reading. The piece Marijen referenced has a lot of good references which gives it credence for me.
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So pharmaceutical companies advertise all the time on their drugs, the alternative companies have to educate the customers direct because doctors don't prescribe their products. We need a once and for all reference that makes the whole process of bone formation, rebuilding and breakdown, clear. It's not even clear is calcium supplements are a good or bad thing.
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I wish we had funding sources for research studies that did not involve the pharmaceutical companies. Then we might get unbiased results and more information on which if the supplements are beneficial to us. We can't even get studies on aspirin because no one wants to fund it. Hoping (but not holding my breath) that the money devoted to the moonshot program will open up funding sources for less biased results.
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Ahhh Kbeee, from your lips as they say. I totally agree with that!
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Never if you are lucky- mine were worst about 1 month in and lasted a while- I found it better to take it at night and I used some Advil for the aches- I toughed it out and I don't feel the side effects now- I'm on the 10 year plan
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I have been on Femara for nearly a month now, I had back pain before starting due to a bulging disc. I can say that either the Femara or maybe the Zoladex has caused my back pain to become worse. I now have hip pain and pain in my right shoulder that has limited my range of motion. Most days I feel sluggish and tired. I try to "push" through each day and am thankful on the days when the pain is less. But... I hate this. I hate these meds. I hate the way they make me feel. I hate being tired all the time. I hate the headaches. I hate not being able to sleep because of the back, hip, and shoulder pain. I used to love to curl up in my bed, next to my husband, and sleep so soundly. I looked forward to that part of my day. Not any more. I dread bedtime. And right now I vacillate between being too hot / too cold so I'm constantly throwing the covers off and putting them back on me. THIS SUCKS!!!
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Owens, I could have TOTALLY written your post. I head back to the ortho tomorrow for the hip pain, and I have to decide when to bring up the right shoulder pain; I try to deal with an issue at a time. I was just discussing with BC friends today how tired I am of being so tired all. the. time. I go to bed at 8:30, and I am still exhausted. I don't have any suggestions, but I do feel your pain. Literally. I can't vent to it to too many people because they just tell me I should be grateful to be alive. I am. Trust me. I just want to feel a little more like me. Vent over. Carry on.
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Anyone that tells you that you should just be grateful to be alive needs to get their head out of their a**!!! Sorry, just needed to vent!
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After radiation my back pain, shoulder pain, hip pain and joint pain was enhanced. They took me off the letrozole for six weeks and things were better. Then I went back on and the first month was fine, but it's all back now, including the kicking off the covers and putting them back on. The sluggish and tired, sometimes headaches in the morning, add trigger thumb and leg pain. Will see the onc in a month but she will want to switch me to tamoxifen I saw it in her notes. No thanks. I walk everyday but it doesn't relieve the pain. The more I do the worse I feel. Exhausted today for no reason. Could it be the radiation back in Feb and March? Before that I was managing.
Kbee,I mentioned my knee pain but didn't push it now I wish I had. Same as you too much at once. Getting denervation for my hip in a few weeks. Steroid didn't help
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KBeee... I just wonder sometimes if it's worth it. Worse case scenario for me is I get BC again and have to do a mastectomy. I'm being monitored with diagnostic mammograms every six months. If something were to develop, more than likely they would catch it early and I could do surgery. A part of me just wants to live out whatever life I have with no meds making me feel bad and if the good Lord chooses to keep me around longer, a big hooray! If not, that's ok too. I'm tired. I want it all to stop.
I know I need to exercise, but just the thought of even trying wears me out! I'm doing my best to eat right, lots of veggies, lower carbs, moderate protein, moderate fat. I'm not going to go out and buy all these vitamins, roots, aroma therapy oils, etc... to try to keep from getting cancer again. Five years down the road, they (whoever THEY are), are going to tell us all those things were actually bad for our bodies. It's a yen/yang, good/evil thing. And my brain is tired of reading about cancer. I'm tired of thinking about it all. I just want to live as best as I can.
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Marijen, do you think shoulder pain is from the radiation? I stopped radiation Mid July. My radiation was on my right side, same side as the pain.
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Yes, I'm sure the shoulder pain is from the radiation. Radiation thightens the tissues, my LE PT told me just the other day. I had alnd 12 nodes removed, one positve, so radiation to under arm and clavicle
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It truly is hard to know the basis of the side effects. Is it the meds? Is it the radiation treatment? Who knows.
I've tried taking pain relievers (over the counter and other). Nothing seems to help. Have you guys found any kind of pain reliever that has helped?
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I was burned horribly during radiation, so I am pretty sure that's the source of my shoulder pain. I do exercise daily; I run and/or walk. My hip pain is actually the worst when I sit. Driving is excruciating. Ibuprofen makes it tolerable. My ortho put me on Meloxicam (Mobic), but it has not helped, and it's flared up GERD and makes me dizzy, so once I see him tomorrow I'll go back to my trusty ibuprofen. Once my kids are out of high school, I may consider dropping the Femera, but since I've already had a recurrence, I know it's way to risky for me to stop. I have 6 more years until they're all done with school, so I'll have to try to tolerate it until then. One day at a time.
Honestly for me, the exhaustion seems to come in waves. Some days I feel horribly depressed and exhausted (have never had depression), and it lasts for about 4 days. Then I seem to snap out o fit for a few weeks. As you may have guessed from my tone today, I'm currently in the midst of one of a funk. Hoping it is better in a few days.
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Kbeee, our funks must be synchronized! It's bad today. Did some laundry, went for a short walk, and changed an appointment. That's it!
Maybe before six years are up there will be a better alternative. I cannot take ibuprofen. And it causes water retention and increases liver enzymes. Maybe not for all.
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owens69...I have the same shoulder pain. And slight back discomfort. I thought it was maybe the actonel I am on for osteoporosis or the Fermara.
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I think the shoulder pain is from the rads because my leftie is where I had it and that is the shoulder that hurts. Also, it has caused some issues with swallowing (it comes and goes) for me as well. I have had cancer twice in my life (once in my 20's - not breast) and so it seems to me that my body likes to make it. I am still taking Femara for now because of the fear that if it happens again, I will not be as lucky (both times were insitu) as I have been. Pain is taking a toll though...
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I spoke with my nurse yesterday who said the shoulder/hip/back pain is from the Femara. She told me to stop taking it for two weeks then they will try me on something else. Makes me nervous...
Is it not enough to just take the Zoladex? Why must we take one of these other meds? Zoladex lowers estrogen, which is a huge benefit.
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